Several species of Clostridium are important to human and animal health. C. difficile, C. perfringens and C. botulinium are commonly known food-contaminating bacteria. The Clostridium bacterium is able to form spores and these spores are able to survive under various conditions. Under some conditions Clostridium difficile bacteria can outgrow and outnumber the normal gut microbiota. Such a condition can be very harmful, causing loss of appetite, diarrhea, abdominal pain and edema of the intestine. This can develop into pseudomembraneous colitis and in rare cases in toxic megacolon. Treatment for C. difficile can be difficult due to its ability as a spore to survive classical antibiotic treatment, which is performed with vancomycin and/or metronidazole. Also a recently introduced antibiotic, fidaxomycin, seems not be active against C. difficile spores. Currently the best approach is via fecal transplantation, where the gut content is replaced by that of a healthy individual. Of course, such a fecal transplantation is more costly, since this has to be performed under close medical surveillance.
The abundance of C. difficile infections has been increasing in the last decades. Infection with this bacterium is the most abundant bacterial infection in health care institutions. Thus, adequate treatment for infections of C. difficile, which especially also affects the spores of C. difficile, is urgently needed.
Next to C. difficile other Clostridum species are known for their toxic effects. C. perfringens is a Gram-positive square-ended anaerobic (microaerophilic) bacillus classified in Group III of the Family Bacillaceae. This non-motile member of the clostridia forms oval, central spores rarely seen in culture unless grown in specially formulated media, although the spores are produced readily in the intestine. Capsules may be seen in smears from tissue. Nitrate is reduced and lecithinase (alpha-toxin activity) can be demonstrated in egg yolk medium (Nagler reaction). Sugar reactions (acid and gas) may be irregular. Food poisoning from C. perfringens gives rise to abdominal pain, nausea and acute diarrhea 8-24 h after the ingestion of large numbers of the organism, a proportion of which survive the acid conditions of the stomach (Sutton & Hobbs, 1971). The illness is usually brief and full recovery within 24-48 h is normal. However, death occasionally occurs in the elderly or otherwise debilitated patients, e.g. in hospitals or institutions (Smith, 1998). The symptoms of the disease are caused by an enterotoxin. C. perfringens is grouped into 5 types A-E according to the exotoxins (soluble antigens) produced. Types A, C and D are pathogens for humans, types B, C, D and E, and possibly A also, affect animals. The enterotoxin produced by types A and C is distinct from the exotoxins and is responsible for the acute diarrhea that is the predominant symptom of C. perfringens food poisoning. The beta-toxin of type C appears to be the necrotic factor in the disease enteritis necroticans jejunitis (“pig-bel”). Type A strains are responsible for gas gangrene (myonecrosis), necrotizing colitis, peripheral pyrexia, septicemia as well as food poisoning.
Botulinum neurotoxin (BoNT) from C. botulinium has the capacity to cause disease in essentially all vertebrates. Symptoms may appear in a few hours or take several days to appear. Initial symptoms such as weakness, fatigue and vertigo, are usually followed by blurred vision and progressive difficulty in speaking and swallowing. In type E botulism nausea and vomiting often occur early in the illness and probably contribute to its lower mortality than types A and B. Disturbed vision and difficulty in speaking and swallowing are due to neurological implications involving extra-ocular and pharynx muscles. Weakening of diaphragm and respiratory muscles also occurs and death is usually due to respiratory failure. Specifically neurotransmission of the peripheral nerve system is blocked. The mortality rate has fallen due to early diagnosis, prompt administration of antitoxin, and artificial maintenance of respiration. The illness is serious and full recovery usually takes many months.
C. tetanus causes one of the major diseases still present in developing countries, tetanus. Tetanus has been known to take up to ten years to manifest, but normally, incubation period is a few days to a few weeks. The first signs of the disease include mild muscle contractions at the site of infection as the infection gradually spreads along nerve fibers to the spinal cord and brain stem. Trismus (lockjaw) ensues with continued rigidity and spasms of the extremities. Death occurs when spasms interfere with respiration.
Clostridium belongs to the Gram-positive bacteria, of which many are known as pathogens. Examples of those pathogenic Gram-positive bacteria are the spore forming Bacillus species, the non-spore-forming bacilli Corynebacterium and Listeria and the sphere-shaped Streptococcus and Staphylococcus. Especially the latter one, of which S. aureus is the most common representative often give lead to bacteria that are multi-resistant (MRSA). Accordingly, new antibiotics that can be used against these bacteria are urgently needed.